This invention relates to a device for concentrating solute-containing solutions, e.g. solvent-containing macromolecular sample solutions, via filtration through a semipermeable membrane, and more particularly to a device which enables the user to obtain various desired retentate concentrations by placing the device in different positions before use. The device of the invention provides rapid concentration of liquid analytical specimens without filtering to dryness.
Effective use of modern analytical techniques for rapid analysis of liquid specimens, particularly biological specimens such as plasma, whole blood, cerebrospinal fluid, or urine, generally requires a small volume of a sample solution which has a concentration of macromolecules which is substantially greater than that of the naturally occurring liquid specimen. Previously, dialysis or ultrafiltration devices such as those described in U.S. Pat. Nos. 3,488,768 and 3,565,256 were used to obtain such sample solutions. However, these devices required expensive auxiliary equipment to induce flow through the membrane, and necessitated the cleaning of the sample chamber after each use.
These difficulties were overcome by the microconcentrator described in U.S. Pat. No. 3,817,379, the disclosure of which is incorporated herein by reference. This microconcentrator is inexpensive and hence disposable, and is capable of providing rapid concentration of samples in short periods of time. This microconcentrator is provided with an impermeable seal coating on the portion of the membrane in contact with the desired final retentate volume. It appears that this coating greatly impedes filtration to dryness, but does not prevent it altogether, due to wicking by surface tension forces, which allows continued filtration after the retentate meniscus recedes onto the coated area. When concentrating small volumes of macromolecules in solution using filtration, e.g. ultrafiltration, there exists the problem of filtration to dryness. Although a fixed volume of buffer may be added to a microvolume concentration device to redissolve macromolecules retained after filtration to dryness, it is generally found that total mass recovery of macromolecules is significantly less, and biological activity recovery is often reduced, as compared to the case when filtration is stopped at the desired final retentate volume. Furthermore, one is unable to obtain various different retentate concentrations using this microconcentrator, unless one uses a method such as having th operator monitor the concentration and withdraw the concentrated sample before filtration stops, using a different microconcentrator for each different retentate concentration desired, etc. These procedures tend to increase the possibility of operator error, and may be uneconomical.
As with the devices of the present invention, the microconcentrator described in U.S. Pat. No. 4,632,761, the disclosure of which is incorporated herein by reference, has a means for preventing filtration to dryness (a "deadstop"). In this microconcentrator device, the filtrate duct or ducts of the membrane support are offset sufficiently inward from the edge of the membrane to enable filtration to stop and a concentrated macromolecular final retentate volume to be obtained when the apparatus is used in a centrifuge rotor and the retentate meniscus reaches the centrifugal radial level of the outermost edge of the outermost filtrate duct. This microconcentrator, unlike the microconcentrator of the invention, requires the use of a centrifuge. Final retentate volume may be varied using the same microconcentrator by selection of centrifuge rotors of differing angles or by variation of the axial alignment of the apparatus in the fixed angle rotor, assuming the filtrate ducts are asymmetric. In the latter case, however, in order to axially align the apparatus in the fixed angle rotor, means, such as a tab positioned on the edge of the membrane support, is required.
Accordingly, it is a principal object of this invention to provide a simple microconcentrator which enables the user to obtain many differing, precisely controlled, retentate concentrations.
It is another object of this invention to provide such a microconcentrator which can concentrate macromolecules or other solutes from a solution without filtering to dryness.
It is a further object of this invention to provide such a microconcentrator that is disposable.
It is a still further object of the invention to provide such a microconcentrator that is economical to manufacture.